Faslodex (fulvestrant) was granted approval by the Food and Drug Administration (FDA) to be used in combination with Verzenio (abemaciclib) – a CDK4/6 inhibitor – to treat patients with HR+/HER2- advanced or metastatic breast cancer who have progressed after endocrine therapy.

The combination was previously approved under Verzenio 's label in September. Both approvals were based on phase 3 results from the MONARCH 2 trial. In 669 women with HR+/HER2- advanced breast cancer, the combination was associated with a statistically significant 7.1-month increase in median progression-free survival (PFS) compared with placebo (16.4 vs 9.3 months).

“This new indication for Faslodex offers another treatment option for women living with HR+, HER2- advanced or metastatic breast cancer with disease progression after endocrine therapy. The study supporting this indication demonstrated that Faslodex used in combination with abemaciclib significantly improves progression-free survival compared to Faslodex and placebo,” Peter A. Kaufman, M.D., Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, said in a statement.

In MONARCH 2, women were randomly assigned to 500 mg of Faslodex and 150 mg of Verzenio (446 patients) or Faslodex plus placebo (223 patients) from August 2014 to December 2015. Eligible patients had progressed during neoadjuvant or adjuvant endocrine therapy, within 12 months of adjuvant endocrine therapy, or during frontline endocrine treatment for metastatic disease. Women were excluded from enrollment if they received chemotherapy, or more than one endocrine therapy in the metastatic setting.

Pre/perimenopausal in the trial received the GnRH agonist goserelin acetate beginning at least four weeks prior to initiation and continuing throughout the study. Patients remained on treatment until development of progressive disease or unmanageable toxicity.

Median age was 60 years and 56 percent of patients were white. All patients had an ECOG performance status of 0 or 1.

The overall response rate (ORR) was 35.2 percent in the experimental arm versus 16.1 percent in the control arm. Investigators observed 14 (3.1 percent) complete responses in the combination arm compared with one (0.4 percent) in the control arm.

More than two-thirds of patients in both groups had a duration of response lasting 12 months. The median duration of response had not been reached in the combination arm, with 90 responders (57.3 percent) continuing to receive treatment at the time of the analysis.

Patients with measurable disease had an ORR of 48.1 percent with the combination compared with 21.3 percent with placebo.

After 12 cycles of treatment, the mean change in tumor size was −62.5 percent in the experimental arm compared with −32.8 percent for placebo. The clinical benefit rate favored the combination, 72.2 percent versus 56.1 percent.

The most common any-grade adverse events (AEs) were diarrhea, neutropenia, nausea, fatigue and abdominal pain. Patients in the combination arm were more likely to develop infection (42.6 percent vs 24.7 percent), but investigators said most infections were grade 1 or 2.

Investigators observed serious adverse events (SAEs) in 22.4 percent of patients in the combination arm and 10.8 percent of patients in the placebo arm. SAEs possibly related to the study drug were more common in the combination arm, 8.8 percent versus 1.3 percent.

Across the study, 24 patients died while receiving therapy or within 30 days of treatment discontinuation, 14 in the Verzenio arm and 10 in the control arm. Three of the deaths — two cases of sepsis and one case of viral pneumonia, all in the combination arm — were related to the study treatment.

The FDA approved single-agent Faslodex in August 2017 for postmenopausal women with HR+/HER2- advanced breast cancer who have not received previous endocrine therapy. The drug had previously been approved as a single agent for HR+ patients following progression on endocrine therapy, and in combination with Ibrance (palbociclib) for the treatment of women with HR+/HER2-negative advanced or metastatic breast cancer who progressed following endocrine therapy.